The Multicentre Selective Lymphadenectomy Trial - 3
United States, Australia, Canada1,500 participantsStarted 2025-10-01
Plain-language summary
The goal of this clinical trial is to demonstrate that there is no difference (non-inferiorty) in the 2 year recurrence-free survival (RFS) between 2 different surgical approaches for clinical Stage III melanoma. Following 6 weeks of standard neaodjuvant immunotherapy, patients will undergo either selective index lymph node resection (ILN) (identified at baseline as the largest affected lymph node) or the standard of care therapeutic lymph node dissection (TLND). The secondary aims are to assess if patients who are managed without TLND will have a reduction in surgical complications (less wound problems \& lymphoedema), an improved quality of life, at a lower healthcare utilisation.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. Male or female patients ≥ 18 years of age at the time of consent
✓. Written informed consent
✓. Cytologically or histologically confirmed, resectable pathological Stage IIIB, C or D (Any T, N1b, N2b, N2c, N3b, or N3c) cutaneous or unknown primary melanoma, with or without primary tumour in situ
✓. A minimum of one macroscopic lymph node, defined as:
✓. Up to 3 satellite (defined as any foci of clinically evident cutaneous and/or subcutaneous metastases occurring within 2 cm of but discontinuous from the primary melanoma) or in-transit metastases (defined as clinically evident cutaneous and/or subcutaneous metastases occurring \>2 cm from the primary melanoma in the region between the primary and the regional lymph node basin) are permitted if they are completely resectable.
✓. Lymph node involvement in the groin (iliac, inguinal or both), axilla or neck only and may be unilateral or bilateral. Concurrent popliteal, epitrochlear or triangular intermuscular space (TIS) nodes permitted, as long as fully resectable.
✓. Tumour amenable to a newly obtained core biopsy of a lesion which has not been previously irradiated. Archival tissue from a past primary or nodal lesion (if applicable) or tissue taken for current diagnosis will also be collected if available.
. Systemic neoadjuvant immunotherapy is scheduled for administration with at least one PD-(L)-1 check point inhibitor (e.g. nivolumab, pembrolizumab, cemiplimab). The immunotherapy regimen may include other checkpoint inhibitors (e.g. ipilimumab, relatlimab, fianlimab). The patient should meet the fitness for treatment requirements as detailed in the relevant regulatory-approved Product Information or Summary of Product Characteristics.
Exclusion criteria
✕. Uveal or mucosal melanoma.
✕. Isolated satellite or in-transit metastases only (without any cytological or histological proven lymph node involvement).
✕. Involvement of any lymph node basin other than groin, axilla or neck. Concurrent popliteal, epitrochlear or triangular intermuscular space (TIS) nodes permitted, as long as fully resectable.
✕. Clinical or radiographic evidence of distant metastasis (any AJCC 8th ed M Stage).
✕. Previous history of lymph node surgery to the same nodal basin, that was more extensive than a sentinel lymph node biopsy (SLNB).
✕. Previous radiotherapy to the same nodal basin.
✕. Any contraindication to the administration of nivolumab, ipilimumab, pembrolizumab or relatlimab per regulatory-approved product information and / or medical oncologist.
✕. Prior anti-PD-1, CTLA-4, PDL-1 or LAG 3 antibody exposure, or an agent directed to another stimulatory or co-inhibitory T-cell receptor for any disease or any chemotherapy or experimental local or systemic drug treatment.